Crystal Structures and Kinetics of S-Nitrosoglutathione Reductase from Arabidopsis thaliana and Homo sapiens

Persistent Link:
http://hdl.handle.net/10150/195575
Title:
Crystal Structures and Kinetics of S-Nitrosoglutathione Reductase from Arabidopsis thaliana and Homo sapiens
Author:
Crotty, Justin William
Issue Date:
2009
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The number of proteins shown to be S-nitrosated in vivo is increasing steadily, highlighting the importance of this redox based post translational modification. S-nitrosoglutathione reductase (GSNOR) reduces S-nitrosoglutathione (GSNO) to GSNHOH, removing GSNO from the cytosol. GSNOR has been linked to asthma in humans and has roles in thermotolerance and disease resistance in the model organism Arabidopsis thaliana. I have studied structure by x-ray crystallography and kinetics by steady state measurements and isothermal titration calorimetry of recombinant GSNOR from both these organisms. I present several structures, including the novel structure of Arabidopsis thaliana GSNOR to 1.4 Å resolution and a ternary complex of human GSNOR with GSNO and NAD+ to 1.5 Å resolution. GSNOR’s apparent ability to reduce GSNO in an environment where the high ratio of NAD⁺/NADH should prevent reductive chemistry from occurring had been unexplained. I present steady state and isothermal titration calorimetry data that demonstrate that GSNOR preferentially binds NADH, with several fold higher affinity than NAD⁺, allowing the enzyme to selectively bind NADH and reduce GSNO.
Type:
text; Electronic Dissertation
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Chemistry; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Montfort, William R.
Committee Chair:
Montfort, William R.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleCrystal Structures and Kinetics of S-Nitrosoglutathione Reductase from Arabidopsis thaliana and Homo sapiensen_US
dc.creatorCrotty, Justin Williamen_US
dc.contributor.authorCrotty, Justin Williamen_US
dc.date.issued2009en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe number of proteins shown to be S-nitrosated in vivo is increasing steadily, highlighting the importance of this redox based post translational modification. S-nitrosoglutathione reductase (GSNOR) reduces S-nitrosoglutathione (GSNO) to GSNHOH, removing GSNO from the cytosol. GSNOR has been linked to asthma in humans and has roles in thermotolerance and disease resistance in the model organism Arabidopsis thaliana. I have studied structure by x-ray crystallography and kinetics by steady state measurements and isothermal titration calorimetry of recombinant GSNOR from both these organisms. I present several structures, including the novel structure of Arabidopsis thaliana GSNOR to 1.4 Å resolution and a ternary complex of human GSNOR with GSNO and NAD+ to 1.5 Å resolution. GSNOR’s apparent ability to reduce GSNO in an environment where the high ratio of NAD⁺/NADH should prevent reductive chemistry from occurring had been unexplained. I present steady state and isothermal titration calorimetry data that demonstrate that GSNOR preferentially binds NADH, with several fold higher affinity than NAD⁺, allowing the enzyme to selectively bind NADH and reduce GSNO.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMontfort, William R.en_US
dc.contributor.chairMontfort, William R.en_US
dc.contributor.committeememberCordes, Matthew H.en_US
dc.contributor.committeememberVierling, Elizabethen_US
dc.contributor.committeememberGhosh, Indraneelen_US
dc.contributor.committeememberWysocki, Vicki H.en_US
dc.identifier.proquest10552en_US
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